4-(4-fluorobenzyl)-N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine-6-oxide | 1226885-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-fluorobenzyl)-N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine-6-oxide
• 英文别名: 4-(4-fluorobenzyl)-N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine 6-oxide；4-[(4-fluorophenyl)methyl]-N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-oxo-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine
• CAS: 1226885-07-9
• 化学式: C₂₅H₂₄FN₅O₂S
• 分子量: 477.562
• InChiKey: TZVQDVLYOIOVLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(4-fluorobenzyl)-N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine 在 间氯过氧苯甲酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以18%的产率得到4-(4-fluorobenzyl)-N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine-6-oxide
  参考文献：
  名称：

  [EN] MODULATORS OF AMYLOID BETA.
  [FR] MODULATEURS DE LA PROTÉINE ?-AMYLOÏDE

  摘要：

  本发明涉及式I的新化合物及其治疗上可接受的盐，它们的药物组合物，制造它们的方法以及它们作为治疗和/或预防各种疾病的治疗方法的使用。特别是，本发明涉及抑制Aβ40和Aβ42产生，增加Aβ37和Aβ38产生并维持Notch信号传导的化合物，并将用于治疗和/或预防与Aβ相关的病理，如阿尔茨海默病、唐氏综合症和β-淀粉样蛋白血管病，例如但不限于脑淀粉样血管病、遗传性脑出血、与认知障碍相关的疾病，例如但不限于MCI（“轻度认知障碍”）、阿尔茨海默病、记忆丧失、与阿尔茨海默病相关的注意力缺陷症状、与阿尔茨海默病或包括混合血管和退行性来源的痴呆在内的疾病相关的神经退行性变、早老性痴呆、老年性痴呆和与帕金森病、进行性核上瘫或皮层基底退行性变相关的痴呆。

  公开号：

  WO2010053438A1

文献信息

• COMPOUNDS 563
  申请人：FORSBLOM Rickard

  公开号：US20100130495A1

  公开（公告）日：2010-05-27

  The present invention relates to novel compounds of formula I and therapeutically acceptable salts thereof, their pharmaceutical compositions, processes for making them and their use as therapeutic methods for treatment and/or prevention of various diseases. In particular the invention relates to compounds, which inhibit the Aβ40 and Aβ42 production, increase the Aβ37 and Aβ38 production and maintain the Notch signaling and will be used for treatment and/or prevention of Aβ-related pathologies such as Alzheimer's disease, Downs syndrome and β-amyloid angiopathy, such as but not limited to cerebral amyloid angiopathy, hereditary cerebral hemorrhage, disorders associated with cognitive impairment, such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

  本发明涉及公式I的新化合物及其治疗上可接受的盐，它们的制药组合物，制备它们的方法以及它们作为治疗和/或预防各种疾病的治疗方法。特别是本发明涉及抑制Aβ40和Aβ42产生，增加Aβ37和Aβ38产生并维持Notch信号的化合物，并将其用于治疗和/或预防与Aβ相关的病理，如阿尔茨海默病，唐氏综合症和β-淀粉样蛋白血管病，如但不限于脑淀粉样血管病，遗传性脑出血，与认知功能障碍相关的疾病，如但不限于轻度认知障碍（MCI），阿尔茨海默病，记忆力丧失，与阿尔茨海默病相关的注意力缺陷症状，与阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆以及与帕金森病，进行性核上性麻痹或皮层基底节变性相关的痴呆。
• Dihydropyridopyrimidines for the treatment of AB-related pathologies
  申请人：AstraZeneca AB

  公开号：US08188101B2

  公开（公告）日：2012-05-29

  Dihydropyridopyrimidine compounds of formula (Ia) and therapeutically acceptable salts thereof, wherein R1, R2 and Z are as defined in the specification; processes for making them and methods for using them in the treatment of Aβ-related pathologies.

  公式（Ia）的二氢吡啶嘧啶化合物及其治疗上可接受的盐，其中R1，R2和Z如规范中所定义；制备它们的过程以及在治疗Aβ相关病理过程中使用它们的方法。
• MODULATORS OF AMYLOID BETA.
  申请人：AstraZeneca AB

  公开号：EP2367826A1

  公开（公告）日：2011-09-28
• US8188101B2
  申请人：——

  公开号：US8188101B2

  公开（公告）日：2012-05-29
• [EN] MODULATORS OF AMYLOID BETA.<br/>[FR] MODULATEURS DE LA PROTÉINE ?-AMYLOÏDE
  申请人：ASTRAZENECA AB

  公开号：WO2010053438A1

  公开（公告）日：2010-05-14

  The present invention relates to novel compounds of formula I and therapeutically acceptable salts thereof, their pharmaceutical compositions, processes for making them and their use as therapeutic methods for treatment and/or prevention of various diseases. In particular the invention relates to compounds, which inhibit the Aβ40 and Aβ42 production, increase the Aβ37 and Aβ38 production and maintain the Notch signaling and will be used for treatment and/or prevention of Aβ-related pathologies such as Alzheimer's disease, Downs syndrome and β-amyloid angiopathy, such as but not limited to cerebral amyloid angiopathy, hereditary cerebral hemorrhage, disorders associated with cognitive impairment, such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

  本发明涉及式I的新化合物及其治疗上可接受的盐，它们的药物组合物，制造它们的方法以及它们作为治疗和/或预防各种疾病的治疗方法的使用。特别是，本发明涉及抑制Aβ40和Aβ42产生，增加Aβ37和Aβ38产生并维持Notch信号传导的化合物，并将用于治疗和/或预防与Aβ相关的病理，如阿尔茨海默病、唐氏综合症和β-淀粉样蛋白血管病，例如但不限于脑淀粉样血管病、遗传性脑出血、与认知障碍相关的疾病，例如但不限于MCI（“轻度认知障碍”）、阿尔茨海默病、记忆丧失、与阿尔茨海默病相关的注意力缺陷症状、与阿尔茨海默病或包括混合血管和退行性来源的痴呆在内的疾病相关的神经退行性变、早老性痴呆、老年性痴呆和与帕金森病、进行性核上瘫或皮层基底退行性变相关的痴呆。